U.S. Pat. Nos. 4,061,779; 4,270,004; and 4,420,639 describe, inter alia, a class of alkyl aralkyl ketones in which the aryl portion of the aralkyl group is a 2-naphthyl group having a specified substituent in the 6-position. These compounds are reported to have anti-inflammatory and/or analgesic activity, and to have the additional advantage of not excessively irritating the stomach at the therapeutic dose. Among the compounds described in these patents is the well known non-steroidal antiinflammatory agent, 4-(6-methoxy-2-naphthyl)-2-butanone, generally known as nabumetone.
While analogous compounds having a double bond in the aliphatic side chain are also reported in these patents to possess the same beneficial properties, it is further reported in the patent that the carbon-carbon double bond tends to impart a degree of oestrogenicity to these compounds. For this reason, the patent recommends using compounds which do not contain the carbon-carbon double bond. Thus the olefinically unsaturated compounds are hydrogenated to saturate the double bond, and thereby provide superior pharmaceuticals.
In Example 20 of the above patents 4-(6-methoxy-2-naphthyl)-3-buten-2-one is prepared in about 41% yield by stirring 6-methoxy-2-naphthaledehyde in excess acetone and approximately 15 mole % aqueous sodium hydroxide, followed by acidification, recovery by ether extraction, and column purification (silica gel column and benzene as eluant). As opposed to the foregoing process in which several co-products are formed in the reaction necessitating tedious separation and purification procedures, it would be highly advantageous if a way could be found for producing 4-(6-methoxy-2-naphthyl)-3-buten-2-one and related substituted 2-naphthyl ketones in an essentially single clean, high conversion and high yield reaction. This invention is deemed to fulfill this need.
Commonly-owned copending application Ser. No. 08/846,220, filed Apr. 25, 1997 by V. Ramachandran and S. E. Belmont describes, inter alia, the synthesis of (alkoxy-substituted 2-naphthyl)-3-buten-2-ones by use of a heterogeneous basic catalyst such as alumina or alkali metal hydroxide in the solid state.